Sulindac and polyp regression

Abstract

Sulindac is useful in regression of adenomatous polyps. In addition to orally administered sulindac, rectal preparations also appear to be efficacious [32]. However, further studies are necessary to determine whether regression of adenomas, the precursor of colorectal cancer, will cause decrease in colorectal cancer risk in both FAP and non FAP patients. Moreover, clinical studies are needed to test the application of this potential chemopreventative drug in several other patient populations. Several interesting observations have been made concerning the use of sulindac. Indomethacin, a related NSAID to sulindac, did not cause polyp regression. Also, upper gastrointestinal tract polyps in the stomach and duodenum appear not to be affected by sulindac therapy. These observations might be explained by the metabolism of sulindac in which the pharmacologically active sulfide metabolite is generated and distributed in the large intestine. Also, investigators noted that after discontinuation of sulindac adenomas recurred. Sulindac treatment was well tolerated at the usual clinical doses. Although some investigators have speculated on the effect of prostaglandin inhibition sulindac on cAMP-dependent mechanisms which control cellular proliferation [33], the cause of adenoma regression is unknown. There is evidence that colorectal endogenous prostaglandin levels decrease with sulindac. Evaluation of colorectal mucosal cellular proliferation in patients treated with sulindac has revealed a decrease in labelling index by bromodeoxyuridine labeling in one study [28] but no change in labelling index by [3H]thymidine incorporation in another investigation [34]. Also, ki 67 labelling index, another measure of cellular proliferation, was not affected in the colorectal mucosa of patients taking sulindac.(ABSTRACT TRUNCATED AT 250 WORDS)